Arthritis & Rheumatism, Volume 63,
November 2011 Abstract Supplement
Abstracts of the American College of
Rheumatology/Association of Rheumatology Health Professionals
Annual Scientific Meeting
Chicago, Illinois November 4-9, 2011.
Lupus Nephritis Susceptibility Markers in PDGRFA-GSX2, SLC5A11, ID4, and HAS2-SNTB1 Regions Identified From a Meta-Analysis of Genome Wide Association Studies of Women with Systemic Lupus Erythematosus.
Chung1, Sharon A., Brown2, Elizabeth E., Williams3, Adrienne H., Bhangale4, Tushar, Ramos3, Paula S., Ziegler3, Julie T., Freedman3, Barry I.
University of California, San Francisco, San Francisco, CA
Cincinnati Children's Hospital Medical Center and the US Department of Veterans Affairs Medical Center, Cincinnati, OH
Johns Hopkins University School of Medicine, Baltimore, MD
University of Pittsburgh, Pittsburgh, PA
Allegheny Singer Research Institute, Pittsburgh, PA
Oklahoma Medical Research Foundation, Oklahoma City, OK
University of Alabama at Birmingham, Birmingham, AL
Wake Forest School of Medicine, Winston-Salem, NC
Genentech, Inc., South San Francisco, CA
King's College London, London, United Kingdom
Feinstein Institute for Medical Research, Manhasset, NY
University of Southern California, Los Angeles, CA
Oklahoma Medical Research Foundation, Center for Genomics and Oncological Research Pfizer-University of Granada-Junta de Andalucia, Oklahoma City, OK
University of California, Los Angeles, Los Angeles, CA
Lupus nephritis (LN) is a clinical manifestation of systemic lupus erythematosus (SLE) resulting from glomerular immune complex deposition and inflammation. LN demonstrates familial aggregation and accounts for significant morbidity and mortality. To facilitate the identification of SLE patients at highest risk for developing LN, we conducted a meta-analysis of three independent genome-wide association studies of SLE.
Through genotyping and imputation, over 2.5 million markers were assessed among 2,001 women with SLE of European descent. SLE cases were considered to have LN if they fulfilled the American College of Rheumatology renal criterion for SLE or had a renal biopsy consistent with LN. Logistic regression adjusting for admixture was computed to test for association between each genetic marker and LN (N=588 LN cases and N=1423 SLE cases without nephritis).
The strongest evidence for association was observed outside the major histocompatibility complex (MHC) including markers localized to 4q11-q13 (PDGFRA-GSX2; OR 3.41; 95% CI 2.15.54; P=2.7×10-7), 16p12 (SLC5A11; OR 2.85; 95% CI 1.934.22; P=3.0×10-7), 6p22 (ID4; OR 0.57; 95% CI 0.460.7; P=4.3×10-7) and 8q24.12 (HAS2-SNTB1; OR 3.15; 95% CI 1.975.03; P=6.2×10-7). Both HLA-DR2 and HLA-DR3, two well established SLE susceptibility loci, showed evidence of association with LN as assessed by their proxies rs9271366 (OR=1.37; 95% CI 1.091.71; P=0.037) and rs2187668 (OR 1.47; 95% CI 1.221.77; P=6.0×10-5), respectively. Within the MHC, a marker in the Class I region, rs9263871 (C6orf15-HCG22), had the strongest evidence of association with LN independent of HLA-DR2 and HLA-DR3 (OR 1.7; 95% CI 1.352.13; P=5.0×10-6).
This study is the first genome-wide investigation of LN, and provides promising evidence for non-MHC markers involved in the development of LN given SLE.
To cite this abstract, please use the following information:
Chung, Sharon A., Brown, Elizabeth E., Williams, Adrienne H., Bhangale, Tushar, Ramos, Paula S., Ziegler, Julie T., et al; Lupus Nephritis Susceptibility Markers in PDGRFA-GSX2, SLC5A11, ID4, and HAS2-SNTB1 Regions Identified From a Meta-Analysis of Genome Wide Association Studies of Women with Systemic Lupus Erythematosus. [abstract]. Arthritis Rheum 2011;63 Suppl 10 :2479